Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors

NCT05278208 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CONNECT2007FD-R-0532-01
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 4

Brief Summary

This study will evaluate the safety and efficacy of Lutathera (177Lu-DOTATATE) in patients with progressive or recurrent High-Grade Central Nervous System (CNS) tumors and meningiomas that demonstrate uptake on DOTATATE PET. The drug will be given intravenously once every 8 weeks for a total of up to 4 doses over 8 months in patients aged 4 to \<12 years (Phase I) or 12 to \</=39 years (Phase II) to test its safety and efficacy, respectively. Funding Source - FDA OOPD (grant number FD-R-0532-01)

Conditions

Embryonal Tumor; Medulloblastoma; Anaplastic Ependymoma; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Primary Central Nervous System Neoplasm; Refractory Diffuse Intrinsic Pontine Glioma; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Primary Central Nervous System Neoplasm; High Grade Glioma; Meningioma; Recurrent Diffuse Intrinsic Pontine Glioma

Keywords

Somatostatin Receptor; DOTATATE; Lutathera

Outcome Measures

Primary Outcomes (4)

• Estimate MTD of Lutathera in pediatric CNS patients 4 to <12 years

  To estimate the maximum tolerated dose (MTD) of Lutathera in pediatric patients between 4 and 12 to \</=39 yearsof age with recurrent and/or progressive high-grade CNS tumors or meningiomas that demonstrate uptake on DOTATATE PET.

  up to 8 months

• Estimate RP2D of Lutathera in pediatric CNS patients 4 to <12 years

  To estimate the recommended Phase II dose (RP2D) of Lutathera in pediatric patients between 4 and 12 to \</=39 years of age with recurrent and/or progressive high-grade CNS tumors or meningiomas that demonstrate uptake on DOTATATE PET.

  up to 8 months

• Calculate the incidence of treatment related adverse events as assessed by CTCAE v5.0 in pediatric (4 to <12 yo) CNS patients treated with Lutathera

  To define and describe the toxicities of Lutathera in pediatric patients with recurrent and/or progressive high-grade CNS tumors or meningiomas that demonstrate uptake on DOTATATE PET. This will include calculating the number of participants with Lutathera-related adverse events as assessed by CTCAE v 5.0

  up to 2 months

• Assess PFS of Lutathera in CNS patients 12 to </=39 years

  To assess efficacy, evaluated by 6 month progression-free survival, of treatment with Lutathera in adolescent and young adult patients age 12 to \</=39 years with recurrent and/or progressive high-grade CNS tumors or meningiomas that demonstrate uptake on DOTATATE PET

  up to 6 months

Secondary Outcomes (2)

• Objective Response Rate of Lutathera in CNS patients 12 to </=39 years

  up to 8 months

• Calculate the incidence of treatment related adverse events as assessed by CTCAE v5.0 in CNS patients 12 </=39 years treated with Lutathera

  up to 8 months

Other Outcomes (3)

• Anti-tumor activity of Lutathera

  up to 8 months

• Prevalence of SST2A expression in patients with different high-grade CNS tumors

  up to 8 months

• Correlation of SST2A expression with clinical and molecular features in high-grade CNS tumor patients treated with Lutathera

  up to 8 months

Study Arms (1)

Phase I-II

EXPERIMENTAL

Pediatric patients (4 to \<12 years, Phase I) and adolescent and young adult patients (12 to \</=39 years, Phase II) with recurrent/progressive high-grade central nervous system tumors and meningiomas that express SST2A and demonstrate uptake on DOTATATE PET will receive Lutathera once every 8 weeks (1 cycle) for a total of 4 doses over 8 months Phase I starting dose will be 200 mCi\*(BSA/1.73m2), corresponding to the BSA-adjusted FDA approved adult Lutathera dosing. The first cycle will be used as the DLT period. Once MTD/RP2D is established, an efficacy expansion cohort of up to 10 patients will be opened to determine the preliminary efficacy of MTD/RP2D of Lutathera Phase II patients will receive the adult RP2D of 200 mCi every 8 weeks to determine the anti-tumor activity of Lutathera in this patient population, through evaluation of 6-month PFS as the primary efficacy endpoint. Response will be assessed on imaging (brain/spine MRI and DOTATATE PET) following every 1-2 cycles.

Drug: LUTATHERA® (Lutetium Lu 177 dotatate)

Interventions

LUTATHERA® (Lutetium Lu 177 dotatate) DRUG

Lutathera: IV administration maximum dose of 200 mCi once every 8 weeks (one cycle) for total of 4 cycles (8 months)

Also known as: Lutathera

Phase I-II

Eligibility Criteria

• Age: 4 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may not qualify if:

• Screening Criteria
• Diagnosis Patient must have a diagnosis of primary high-grade CNS tumor (any histopathologic diagnosis that is WHO grade III-IV) or meningioma (any histologic grade) that is recurrent, progressive, or refractory. Note that patients with DIPG (based on radiographic/clinical diagnosis) who have undergone biopsy will be eligible with histologic diagnosis of grade II-IV infiltrating glioma. All tumors must have histologic verification either at the time of diagnosis or recurrence, except for patients meningioma who have not previously undergone biopsy or resection.
• Note: Refractory disease is defined as the presence of persistent abnormality on conventional MRI that is further distinguished by histology (biopsy or sample of lesion) or advanced imaging, OR as determined by the treating physician and discussed with the primary investigator prior to enrollment.
• Prior Therapy Patients must have recurred/progressed following prior standard therapy for their tumor. Note: Patients with meningioma, atypical meningioma, or anaplastic meningioma must have received at least surgical resection or radiation.
• Screening Consent Participant/legal guardian is willing to sign a screening consent for \[68Ga\]Ga-DOTATATE PET imaging. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines.
• Eligibility Criteria
• Phase I Age Patient must be ≥ 4 and \<12 years of age at the time of enrollment. Disease Status: Patients who participate in the efficacy expansion cohort must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions Patients with measurable extraneural disease only are also eligible.
• Phase II Age Patient must be 12 to \</=39 years at the time of enrollment.
• Uptake on \[68Ga\]Ga-DOTATATE PET Patients must have uptake on DOTATATE PET/CT in at least one tumor lesion (corresponding to known disease) equivalent to a Krenning score ≥2 (confirmed by central radiology review).
• Prior Therapy Patients must have recovered from the acute treatment related toxicities (defined as ≤ grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to entering this study.
• Chemotherapy Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea.
• Investigational/Biologic Agent
• ●Biologic or investigational agent (anti-neoplastic): Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment.
• For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
• ●Monoclonal Antibodies and agents with known prolonged half-lives: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.

Sponsors & Collaborators

• Nationwide Children's Hospital: lead

Study Sites (4)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

WITHDRAWN

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43235, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

NOT YET RECRUITING

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MeSH Terms

Conditions

Glioma; Meningioma; Neoplasms, Germ Cell and Embryonal; Medulloblastoma; Ependymoma; Diffuse Intrinsic Pontine Glioma; Central Nervous System Neoplasms

Interventions

lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases; Neuroectodermal Tumors, Primitive; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases

Study Officials

• Margot Lazow, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelsey H Troyer, PhD

CONTACT

614-722-8566; kelsey.troyer@nationwidechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase I (4 to \<12 yrs) Lutathera (maximum dose of 200 mCi) once every 8 weeks (one cycle) for 4 cycles. Level 0: 150 mCi\*(BSA/1.73m2). Level 1#: 200 mCi\*(BSA/1.73m2). Level 2: 250 mCi\*(BSA/1.73m2). #starting dose Phase II (12 to \</=39 years) RP2D 200 mCi once every 8 weeks

Study Record Dates

• First Submitted: February 7, 2022
• First Posted: March 14, 2022
• Study Start: November 21, 2022
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2033
• Last Updated: April 13, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)